For example, about 75% of CFC patients have gain-of-function (GOF) variants in the B-RAF gene, and GOF variants in K-RAS, MEK1 and MEK2 are also found in some affected individuals (Aoki et al., 2008; Bustelo et al., 2018; Dard et al., 2018). Here, BRAF is linked to cardiofaciocutaneous syndrome.